PRMT2 Affects Tamoxifen Resistance In Breast Cancer Cell Via The MAPK/ERK Pathway

Objective: To investigate the effect of PRMT2 on tamoxifen resistance in MCF-7 cells and MDA-MB-231 cells and to explore the underlying mechanisms.Method: Efficiency of PRMT2 shRNA was confirmed by qPCR. MCF-7-PRMT2-KD cell line was confirmed by qPCR and Western blot. Flow Cytometry was carried out to analyze the effect of TAM and PRMT2 on breast cancer cell dead. Western Blot analysis was used to detect the effect of TAM on PRMT2、ER-ɑ36 and P-ERK1/2 expression in breast cancer cells.Result:1. PRMT2 shRNA and MCF-7-PRMT2-KD was confirmed.2.The MCF-7-PRMT2 cell lines were treated with 7.5μmol/L of TAM for 4 hours, Flow cytometry results showed that TAM concentration group had a increasing dead rate,and suggested that MCF-7-PRMT2 with high expression of PRMT2 had a increasing dead rate.TAM and PRMT2 could enhance the dead rate(P <0.05).3.Western blot analysis revealed that in the MCF-7 cell line which was more sensitive to the TAM,after treated cells with TAM(2μmol/L) at the different time points(0、half hours、one hours、two hours 、four hours), the protein levels of PRMT2 were upregulated by tamoxifen, on the other hand, the protein levels of P-ERK1/2 were downregulated by tamoxifen,and the protein levels of ER-ɑ36 in this cell line had no obvious change. In contrast, in the MDA-MB-231 cell line which was resistant to TAM, the protein levels of PRMT2 were downregulated by tamoxifen, on the other hand, the protein levels of P-ERK1/2 were upregulated by tamoxifen, Besides, unlike the MCF-7 cell line, the protein levels of ER-ɑ36 in such drug-resistant cell line had increased.4. Western blot assay showed that P-ERK1/2 were obviously downregulated with over expression of PRMT2, on the other hand, P-ERK1/2 were obviously upregulated with low expression of PRMT2.Conclusion:1. MCF-7-PRMT2-KD stable cell lines were availably established.2. PRMT2 can increase the sensitivity of TAM in MCF-7 cells, its mechanism may be related to downregulate the expression of P-ERK1/2.3. In MDA-MB-231 cells, the TAM could downregulate the expression of PRMT2, upregulate the expression of ER-ɑ36 and phosphorylation level of ERK1/2.